Biology subjects

Fischer, J.

Publications and source records attributed to Fischer, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Copulation calls indicate fertility but do not reflect female mate competition in wild Guinea baboons

Across different modalities, signals play a core role in attracting mates and influencing mating success. In several non-human primate species, females produce calls during mating that are thought to promote male competition over receptive females. The extent to which social system characteristics modulate the function of copulation calls remains less clear. We studied copulation calls in wild Guinea baboons (Papio papio), who live in a multilevel society structured around units in which females associate and mate almost exclusively with a single male. We hypothesised that females use copulation calls as an indirect form of mate competition, with competition increasing in larger units. In addition, we hypothesised that females are more likely to mate again after calling. We analysed 6116 copulations between 2014 and 2025, involving 99 reproductively active females and 78 subadult and adult males. Females produced copulation calls in 72.7% of copulations, with large inter-individual variation. Neither unit size nor its interaction with the female's swelling size or the presence of simultaneously receptive females affected the probability of calling. A survival analysis with a subset of the data (2353 copulations) revealed no effect of calling on the latency to the next mating. Our results render the hypothesis that female Guinea baboons use calls in indirect mate competition unlikely. Yet, the probability of calling varied with sexual swelling size, suggesting that calls signal female fertility. Possibly, Guinea baboon copulation calls represent an evolutionary remnant, no longer under selective pressure, and can be considered index signals of female fertility.

animal behavior and cognition↗

bioRxiv2026

Large-scale, interpretable gene regulatory network inference through biologically informed matrix factorization

Gene regulatory networks (GRNs) provide a mechanistic framework for understanding how transcription factors coordinate gene expression to establish cellular identity and phenotype. Methods that integrate gene expression with motif-derived regulatory priors and other sources of biological information have substantially advanced gene regulatory network inference by reconstructing condition-specific regulatory architecture. These approaches estimate the evidence supporting regulatory interactions and have proven remarkably successful in a wide range of biological applications. A complementary view of regulatory networks, however, seeks to estimate the effect of those interactions on gene expression itself, providing a framework in which regulatory edges can be interpreted as activating or inhibitory influences on transcription. We developed Giraffe, a biologically informed matrix factorization framework that jointly estimates transcription factor activities and gene regulatory networks by integrating gene expression, motif-based regulatory priors, and transcription factor protein-protein interactions. Giraffe estimates signed partial regulatory effects whose magnitude and sign can be interpreted as the strength and direction of transcriptional regulation. Building directly on the biological framework established by methods such as PANDA, Giraffe provides a complementary representation of gene regulatory networks that emphasizes mechanistic interpretation while remaining scalable, flexible, and computationally efficient. Across synthetic benchmarks, six human tissues, yeast transcription factor perturbation experiments, and liver hepatocellular carcinoma, Giraffe accurately reconstructs regulatory interactions while distinguishing activating from inhibitory regulation with high accuracy. The inferred networks recover known features of tissue-specific regulation, correctly classify regulatory effects in transcription factor perturbation experiments, and identify biologically coherent changes in regulatory programs associated with liver cancer. Together, these results demonstrate that estimating the direction of transcriptional regulation provides a complementary perspective on gene regulatory networks that facilitates biological interpretation and hypothesis generation.

systems biology↗

bioRxiv2026

Microbial, dietary insect, and pathogen communities in fresh and decomposing guano of anthropic little brown bat (Myotis lucifugus) maternity colonies

The guano of insectivorous bats holds ecological information that can be assessed non-invasively to characterize the gut microbiome and diet, alongside environmental microbes and pathogens of conservation concern. Despite this potential, how guano communities change during decomposition remains understudied, particularly inside anthropic roosts rather than caves. In this study, guano from little brown bat (Myotis lucifugus) colonies was sampled monthly across the summer maternity season from three sites across two locations in Connecticut, USA, at fresh deposition and at 4, 8, and 12 weeks following deposition. Resolving these cross-kingdom signals required five workflows: short-read 16S and ITS2 amplicon sequencing (Illumina) for bacterial and fungal profiling, long-read CO1 metabarcoding (Oxford Nanopore) for arthropod diet in fresh samples, long-read shotgun metagenomics for viral identification in aged samples, and targeted qPCR for organisms of bat, human, and forest-health concern. Fresh guano generated a consistent bacterial signal across sites, whereas fresh fungal communities differed by site. Responses to decomposition depended on roost setting: exterior sites lost fungal diversity and shifted toward environmental aerobes over time, while the interior roost retained the fresh sample profile. Dietary composition varied temporally, was dominated by Diptera, and included the invasive emerald ash borer (Agrilus planipennis). Pseudogymnoascus destructans, the causal agent of white-nose syndrome, occurred in fresh and aged samples at all three sites but persisted for 12 weeks only at the interior roost, where antifungal bacterial taxa were depleted. Long-read shotgun metagenomics of aged guano recovered roughly 100 viral species, predominantly bacteriophages, alongside non-bacteriophage mastadenoviruses associated with humans, bats, and other mammals. These results show that anthropic structures influence the trajectory of guano microbiome succession, and that maternity colony guano enables non-invasive assessment of environmental pathogens, bat diet, and bacterial and fungal communities.

ecology↗

bioRxiv2026

Fast and Luminous: CLIP-tag2

CLIP-tag is a self-labeling protein tag used for the specific fluorescence labeling of proteins. However, its low labeling speed and the poor cell permeability of its substrates result in low labeling efficiencies in live-cell applications. Here, we introduce a substrate optimized for live-cell applications, as well as an engineered CLIP-tag variant, CLIP-tag2, which reacts with the new substrate almost 1000-fold faster than the original CLIP-tag-substrate pair. CLIP-tag2 fusion proteins can be specifically and efficiently fluorescently labeled in cells within minutes at nanomolar substrate concentrations, and can be multiplexed with other self-labeling tags such as SNAP-tag2 and HaloTag7. These advances establish CLIP-tag2 as a powerful tagging platform for high-performance live-cell bioimaging.

biochemistry↗

bioRxiv2026

Diversity and spatiotemporal activity patterns of medium and large mammals in the Niokolo-Koba National Park, Senegal

West African savannahs provide habitats to diverse species assemblages, yet remain understudied compared to their East and Southern African counterparts. The Niokolo-Koba National Park in southeastern Senegal constitutes one of the largest remaining protected areas in West Africa and supports a mosaic of savannah and forest habitats with a diverse assemblage of medium- and large-sized mammals. Here, we analysed camera-trap data originally collected to monitor predator presence in the northwestern sector of the National Park. We deployed 37 cameras across 37 km{superscript 2} from February 2022 to March 2023, resulting in 13,161 camera-trap-days. We assessed alpha diversity indices and spatiotemporal activity patterns of large and medium-sized mammals across habitat types. Evenness values - the degree to which species abundances are distributed uniformly within a community - were higher in the savannah than in forest habitats, although overall species richness was comparable. In contrast, animal sighting rates were higher in forests than in savannahs. Estimated diel activity mostly corresponded with established species-specific behavioural patterns. Our analyses revealed differential use of certain habitat types across the day, likely driven by spatially segregated sleeping sites and foraging locations. Our results provide a reference for future studies and monitoring efforts and highlight the value of the forest-savannah mosaic for the local species assemblage within the larger ecosystem of Niokolo-Koba National Park.

ecology↗

bioRxiv2026

Post-mortem infant-directed behaviours in wild Guinea baboons

The growing field of comparative thanatology aims to shed light on how and why the understanding of death evolved. Observations across different nonhuman primate species have reported care-taking behaviour of dead infants, but also cannibalism. Various hypotheses have been put forward to explain these infant-directed behaviours, ranging from responses to infantile cues to an understanding of death. To aid comparative analyses and test some of these hypotheses, we report behaviours directed at dead infants in a wild population of Guinea baboons (Papio papio) living in the Niokolo-Koba National Park, Senegal. During 12 years of field observations (2014-2025), 67 infants died before reaching 1 year of age. In 4 cases, we could not establish when the infants had died because the field station was closed due to the COVID-19 pandemic. In 22 of the remaining 63 cases, mothers, but occasionally also other group members, carried, protected, groomed, and dragged dead infants. In 6 cases, cannibalism occurred. None of the mothers expressed any signs of emotional distress in response to infant death. We suggest that a concept of death in Guinea need not be invoked to explain the observed behaviours. Instead, selection appears to have favoured post-mortem caretaking behaviours to avoid abandoning an infant that might temporarily be unresponsive. The lack of infant responses to maternal behaviour and the disintegration of the corpse may drive the transition from perceiving the infants as an object that evokes caretaking to one that resembles food, which ultimately facilitates occurrences of cannibalism.

animal behavior and cognition↗

bioRxiv2026

Maternal style does not predict infant growth and survival in wild Guinea baboons

Primate infants depend on their mothers for nursing, transportation, and survival, but also benefit from other behaviours such as contact, protection, and the mother serving as a model for social learning. During infancy, variation in maternal care ("maternal style") can have profound consequences for infant development and survival. We investigated the link between maternal style and infant growth and survival in wild Guinea baboons (Papio papio). This species lives in a tolerant social system with female-biased dispersal. We used data from N = 80 infants to assess variation in maternal style. The final statistical models comprised data from N = 50 infants for the growth analysis based on Parallel Laser Photogrammetry (PLP) measures of forearm length, and N = 63 infants for the survival analysis. To account for heterogeneity in data, we applied a recently established statistical framework that controls for variation in maternal behaviour with infant age. We found only moderate variation among mothers and no evidence for a link between maternal style and infant growth or survival. Neither infant sex, maternal age, nor NDVI variation, a measure later shown to be a poor indicator of food availability, predicted infant growth or survival. We suspect that, in this population living in a habitat with high carrying capacity, disease and predation have greater effects on infant growth and survival than maternal behaviour. Future studies should consider the interplay between infant behaviour and maternal responses in greater detail to better understand variation in early social development.

animal behavior and cognition↗

bioRxiv2025

High-resolution microCT reveals relationships between stomata and interior leaf anatomy in Sorghum

Stomata are pores in the leaf epidermis that regulate the trade-off between CO2 uptake for photosynthesis and water vapor loss to the atmosphere. Stomatal patterning therefore influences water use efficiency and is a target for engineering to avoid drought stress. However, there is limited understanding of how internal leaf anatomy is coordinated with stomatal development, in part due to the technical challenges of assessing three-dimensional anatomy with sufficient resolution. C4 grasses are understudied, and this is a significant knowledge gap given their file-like stomatal distribution and unique mesophyll organization. In this study, wild-type sorghum and a low-stomatal density transgenic line expressing a synthetic Epidermal Patterning Factor (EPFsyn) were studied. High-resolution microCT was paired with machine learning to characterize three-dimensional traits of mesophyll, epidermis, and airspace, which together determine gias. Sorghum internal leaf airspace is an arrangement of large sub-stomatal airspaces with thin air passageways. Adaxial and abaxial surfaces differed in stomatal patterning relative to mesophyll structures, sub-stomatal crypts and airspace CO2 conductance (gias). Surprisingly, adaxial stomata were consistently located above rather than between vascular bundles. Unexpectedly, gias was not significantly different in wild-type versus EPFsyn. EPFsyn plants had larger crypts and shifts in internal leaf anatomy, indicating a potential compensation mechanism for predicted impacts of reduced stomatal density on gias. These findings provide a new understanding of the interplay between leaf surface specific anatomy and internal structural patterning of the mesophyll in a C4 species, and provides knowledge relevant to engineering water use efficiency in crop species.

plant biology↗

bioRxiv2025

A membrane-driven biochemical oscillator tunable by the volume to surface area ratio

Oscillations are ubiquitous features of biological organisms, playing crucial roles in processes from circadian rhythms to developmental patterning. Protein-based biochemical oscillators have particular applications in synthetic biology because they can access fast and slow timescales that are independent from the transcription-translation machinery required of genetic oscillators. Here, we introduce and model such a mass-conserving biochemical oscillator using mass-action reaction kinetics that exploits dynamic changes to membrane phospholipid concentrations to drive proteins on and off the membrane in robust, tunable rhythms. Importantly, the oscillations rely on amplification of reactions on the membrane via dimensional reduction, and they are therefore tunable by variations in the volume-to-surface area ratio (V/A) of the system. With components inspired by the endocytic machinery, we show that a wide range of physiologically relevant biochemical rates can produce oscillations in part due to this independent geometric control. A broad computational screen of the high-dimensional parameter space reveals that oscillations require relatively strict enzyme kinetic design rules for low V/A but much more permissive kinetics for larger V/A. We validate that oscillations persist with more realistic reaction-diffusion simulations that captures explicit diffusion and stochastic, integer valued copy numbers, in overall good agreement with the period and amplitude of the deterministic oscillators. Because the oscillations rely on time-dependent changes to the surface properties and not post-translational modifications to the protein subunits, we demonstrate that it can be coupled to a self-assembling trimer, driving not only changes in localization but trimer yield. Our analysis establishes this membrane-localization oscillator as a new, geometry tunable and programmable timing module and suggests a potential for geometry sensing in engineered or cell-free systems.

biophysics↗

bioRxiv2025

Nested Male Reproductive Strategies in a Tolerant Multilevel Primate Society

Male reproductive success varies within populations. Models explaining reproductive skew emphasise dominance, yet the determinants of male reproductive success in egalitarian societies remain poorly understood. Using nine years of behavioural and genetic data from five parties, we investigated male reproductive monopolisation in wild Guinea baboons (*Papio papio*), an egalitarian multilevel society with one-male "units" nested within "parties" and low male-male contest competition. Genetic analyses showed 93% of the 71 infants were sired by the female's "unit male", with extra-unit paternities consistent with limited control models. Reproduction was distributed among multiple unit males, resulting in low reproductive skew at the party level, with top males siring 23-40% of offspring, well below levels in despotic species. Female takeovers were rare, suggesting male restraint. Among prime-aged males, the number of unit females was only weakly positively associated with dominance ratings. Prime-age predicted reproductive success better than dominance. Non-prime-aged males had fewer females across dominance ratings. In conclusion, male Guinea baboons' reproductive potential is shaped less by dominance than by age and stable associations with females, who play an active role in inter-sexual relationships. These results emphasise the need to move beyond frameworks focused solely on dominance-based mechanisms and to consider species-specific social organisation.

animal behavior and cognition↗

bioRxiv2025

Rapid updating of ecological information in wild Guinea baboons

Knowing where to find what kind of food when is essential for survival and reproduction. Recent links between feeding ecology and brain size have revived interest in foraging cognition as a core component in cognitive evolution. We investigated whether free-ranging Guinea baboons (Papio papio) keep track of the spatio-temporal availability of a preferred food resource, the Natal orange (Strychnos spinosa). A natural experiment, a massive wildfire that destroyed most oranges in 2019, allowed us to disentangle habitual routines from goal-directed behaviour in the baboons. The animals space-use patterns shifted significantly following the wildfire. After one single visit, they stopped going to the area during the period when Natal oranges would normally be available. In the following year, they resumed regular space-use patterns. We also assessed travel linearity, speed, and departure time from sleeping sites towards the target area with and without ripe fruit. Guinea baboons travelled more linearly, 14% faster, and ~40 minutes earlier towards the target area when S. spinosa was in season compared to when it was not. In conclusion, Guinea baboons rapidly updated their knowledge of high-value food availability and adjusted their space-use accordingly. These results underscore their capacity for flexible decision-making and goal-directed foraging.

animal behavior and cognition↗

bioRxiv2025

Elevated IL-1 beta plasma levels, altered platelet activation and cardiac remodeling lead to moderately decreased LV function in Alzheimer transgenic mice after myocardial ischemia and reperfusion

IntroductionNeurodegeneration and dementia are key factors in Alzheimers disease (AD). The deposition of amyloid-{beta} into senile plaques in the brain parenchyma and in cerebral vessels known as cerebral amyloid angiopathy (CAA) are the main clinical parameters of AD. Acute myocardial infarction (AMI) and AD share a comparable pathophysiology. In detail, AMI survivors have a higher risk of vascular dementia and AD patients with AMI face a poor prognosis with a high rate of major adverse cardiovascular events. High blood levels of amyloid-{beta}40 are identified in patients with high risk for cardiovascular death. However, the underlying mechanisms and the consequences of AMI in AD patients are unclear to date. MethodsAD transgenic APP23 mice were analysed in an experimental AMI using the closed-chest model. ResultsAPP23 mice displayed significantly decreased left ventricular function as detected by FS/MPI (fractional shortening/myocardial performance index) after 24 h and 3 weeks after ligation of the LAD compared to WT controls. No differences have been observed in infarct and scar size. However, the analysis of cardiac remodeling after 3 weeks showed an altered composition of the collagen tissue of the scar with elevated tight but reduced fine collagen in APP23 mice. Altered scar formation was accompanied by elevated degranulation of platelets following activation of the collagen receptor GPVI. ConclusionThe here presented results suggest that AD patients are at higher risk for cardiac damage after AMI that might increase the risk for cardiovascular death. This implies the need of a personalized therapy of AMI in AD patients.

neuroscience↗

bioRxiv2025

Disparate social structures are underpinned by distinct social rules across a primate radiation

Over six decades of research on wild baboons and their close relatives (collectively, the African papionins) have uncovered substantial variation in their behavior and social systems. While most papionins form discrete social groups (single-level societies), a few others form small social units that are nested within larger supergroups (multi-level societies). These two systems are generally thought to be qualitatively distinct, but data from wild populations increasingly suggest that there may be areas of overlap. To quantify this potential gradient in social structure, a more systematic, comparative analysis is needed. Here, we constructed a database of behavioral and demographic records spanning 135 group-years, 28 social groups, 13 long-term field studies, and 11 species to quantify variation in grooming network structure, and identify the individual and dyadic properties (e.g., kinship and social status effects) that underlie this variation. Consistent with accumulating observations in the field, the single-level species could be divided into two categories: cohesive and cliquish. Cohesive single-level networks were dense, kin-biased, and moderately rank-structured, while cliquish single-level networks were more differentiated, slightly more kin-biased, and strongly rank-structured. As expected, multi-level networks were very modular and shaped by females ties to specific dominant males but varied in their kin biases. Taken together, these data suggest that (i) kin and rank biases are widespread but vary in their strength; (ii) male-centered subgroups are exclusive to multi-level systems; and (iii) increases in network modularity can emerge in response to heightened nepotism and male-centered clustering. SIGNIFICANCE STATEMENTWhat forces explain variation in primate societies? While kinship and dominance shape the social lives of many of our close relatives, it is unclear how their effects differ across species. Using a new database comprising decades of field research, we found that baboons and their close relatives fell into three general patterns: one in which groups were cohesive, kin-biased, and moderately rank-biased, another in which groups were more cliquish and nepotistic, and a third in which groups were divided into clusters centered on dominant males. Distinct primate societies may thus reflect differences in the strength of females nepotistic biases and the degree of males social influence.

animal behavior and cognition↗

bioRxiv2025

Peripheral T Helper Cells Dominate the Synovial CD4⁺ T Cell Compartment in Systemic Juvenile Idiopathic Arthritis and Are Shaped by IL-1β and IL-18

ObjectivesSystemic juvenile idiopathic arthritis (sJIA Stills disease) is primarily driven by systemic autoinflammation but can progress to chronic arthritis, implicating dysregulated adaptive immunity. However, the molecular mechanisms within inflamed joints that link innate and adaptive immune activation remain poorly defined. This study aimed to define the transcriptional and clonal landscape of synovial CD4+ T cells in sJIA and to identify inflammatory signals driving their differentiation. MethodsSynovial fluid CD4+ T cells from patients with sJIA and oligo/polyarticular JIA (o/p-JIA) were analyzed using flow cytometry, scRNA and TCR sequencing. Cytokine secretion and B helper function were assessed in vitro. The effects of IL-1{beta} and IL-18 on T cell differentiation were evaluated using bulk RNA sequencing and multiplex ELISA. ResultssJIA joints harbored a dominant population of clonally expanded CD4+ T cells with a peripheral T helper (Tph) cell state, marked by IL-21 and CXCL13 expression and robust B cell help. scRNA-seq revealed a heterogeneous CD4+ T cell landscape, with transcriptional convergence of Tph and regulatory (Treg) programs particularly in sJIA. A subset of these cells exhibited molecular features consistent with differentiation from Tph precursors. In vitro, IL-1{beta} and IL-18 promoted Tph differentiation, aligning with the transcriptional profiles of expanded effector Tph cells observed in sJIA joints. ConclusionThese findings identify Tph cell-driven adaptive immunity as a key feature of chronic arthritis in sJIA and link IL-1{beta} and IL-18 to Tph cell induction. This challenges the classical autoinflammatory paradigm and suggests that early cytokine-targeted therapy may modulate T cell fate and disease course.

immunology↗

bioRxiv2025

A Transient Increase in Cardiomyocyte Protein O-GlcNAcylation Enhances Susceptibility to Pressure Overload-Induced Cardiac Remodeling

BACKGROUNDThe observation that diabetic patients always under tight-glycemic control consistently show better cardiovascular disease outcomes compared to patients who transition to tight-glycemic control after prior conventional glycemic control lead to the concept of metabolic memory. Mechanisms such as epigenetics possibly mediate the lasting metabolic memory effects, our understanding of the underlying mechanisms remains limited. Increased cardiac protein posttranslational O-linked {beta}-N-acetylglucosamine (O-GlcNAc) modification is implicated in cardiac remodeling observed in diabetes, and our previous work shows chronically elevated cardiomyocyte O-GlcNAc causes adverse cardiac changes. Therefore, the current study hypothesized that transiently increased cardiomyocyte O-GlcNAcylation leads to exacerbated adverse cardiac remodeling after subsequent pressure-overload. METHODS AND RESULTSUsing our previously described inducible cardiomyocyte specific, dominant-negative O-GlcNAcase (dnOGAh) mouse and single transgenic littermate controls (Con), we induced O-GlcNAc levels for 2wk (ON), followed by a 2wk washout (OFF); mice then underwent transverse-aortic constriction (TAC) or Sham surgery. We observed the expected cardiac remodeling in TAC groups, including decreased cardiac function, and increased hypertrophy and fibrosis. Moreover, these pathologic measures were exacerbated in the ON/OFF-TAC vs. Con-TAC mice; additionally, transcriptomic analysis of LV-tissue from each experimental group showed pathways which not only supported our fibrosis, hypertrophy and functional results of exacerbated cardiac remodeling, but also, revealed potential novel molecular pathways underlying this pathologic remodeling. CONCLUSIONSWe observed exacerbated cardiac pathology between ON/OFF-TAC vs. Con-TAC groups supporting the concept of "O-GlcNAc memory" as a component of metabolic memory. Moreover, transcriptomic analysis provides insight into potential molecular pathways underpinning this metabolic/O-GlcNAc memory such as Ccn2/CTGF-driven fibrosis, and/or Nox4-driven oxidative stress. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/657956v1_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@717ea9org.highwire.dtl.DTLVardef@132bdcaorg.highwire.dtl.DTLVardef@4a2bdaorg.highwire.dtl.DTLVardef@18508d9_HPS_FORMAT_FIGEXP M_FIG C_FIG Clinical PerspectiveO_ST_ABSWhat is new?C_ST_ABSO_LIWe provide a novel paradigm to study phenotypic and molecular effects of specific, transiently increased cardiomyocyte O-GlcNAcylation on the heart. C_LIO_LIOur results show exacerbated adverse cardiac remodeling due to transiently increased cardiomyocyte O-GlcNAc with pressure-overload, supporting the concept of "O-GlcNAc memory" as a component of metabolic memory. C_LIO_LITranscriptomic insights show gene expression basis for not only observed exacerbated adverse cardiac remodeling (e.g., hypertrophy, fibrosis, cardiac dysfunction), but also potential molecular pathways that could drive cardiac pathology exacerbation of O-GlcNAc memory. C_LI What are the clinical implications?O_LIThis study supports a concept of "O-GlcNAc memory", where previously increased cardiomyocyte protein O-GlcNAcylation can impact the later development of differential cardiac pathology--like the pathology seen in metabolic memory research. C_LIO_LIThe potential role of O-GlcNAc in mediating metabolic memory will help focus future translational research on this modification and downstream cardiac effects in diabetes. C_LIO_LITranscriptomic profiling of cardiac remodeling in this model provides an investigational roadmap for future molecular and functional studies to identify novel therapeutics that ameliorate heart disease induced by differential metabolic memory. C_LI

molecular biology↗

bioRxiv2025

CSF single-cell RNA sequencing reveals clonally expanded CD4+ stem cell-like memory T cells in GAD65-antibody associated neurological syndromes

BackgroundGlutamic acid decarboxylase (GAD) antibody-associated autoimmune neurological syndromes (AINS) are a spectrum of autoimmune-mediated CNS disorders. While antibodies targeting the 65 kDa isoform of GAD are of high diagnostic value, T cell mediated cytotoxicity has been identified as a key component of disease pathogenesis. The precise pathophysiological mechanisms by which the disease is triggered and maintained, however, remain incompletely understood. MethodsWe performed single-cell transcriptome and immune repertoire sequencing (sc-seq) in CSF and blood of 8 anti-GAD65 AINS patients compared to 8 non-inflammatory controls. Monoclonal antibodies (mAbs) were synthesized from B cell receptor (BCR) data to evaluate the B cellular immune response. FindingsWe identified an increase and expansion of activated CD4+ stem cell-like memory T cells (TSCM) in the CSF of anti-GAD65 AINS patients. Expanded T cells showed increased expression of proinflammatory genes. The mAb analysis revealed a high frequency of GAD65-reactive BCRs in the CSF of anti-GAD65 AINS patients with increased somatic hypermutations compared to non-GAD-reactive BCRs and BCRs from controls. ConclusionsSc-seq identified clonally expanded CD4+ TSCM in the CSF of anti-GAD65 AINS patients harboring cytotoxic properties likely contributing to disease pathogenesis. GAD-reactive B cells circulate in the CSF of anti-GAD65 AINS patients further supporting the concept of an antigen-specific intrathecal immune response. Future studies need to clarify the actual pathogenicity of these immune cells and the link between T and B cellular immune mechanisms in the pathogenesis of anti-GAD65 AINS. FundingGerman Research Foundation (ERARE18-202 UltraAIE), German Federal Ministry of Education and Research (CONNECT GENERATE (2.0); 01GM1908A and 01GM2208A).

immunology↗

bioRxiv2025

Social evaluation of skilfulness in Tonkean macaques (Macaca tonkeana) and brown capuchins (Sapajus apella)

For optimal decision-making, social animals can benefit from evaluating others behaviours. Some species seemingly consider the skills of others when deciding who to interact with in different contexts. Yet, whether and how nonhuman animals form impressions about others competence is still unclear. In this study, we investigated whether Tonkean macaques (Macaca tonkeana) and brown capuchins (Sapajus apella) can evaluate the skilfulness of others. Subjects observed two human actors (one skilful, one unskilled) trying to open several food containers. Only the skilful actor successfully opened the containers and released food so the experimenter could give it to the subjects. Afterwards, subjects did not choose the skilful actor significantly more frequently than the unskilled one. Their choices for the skilful actor did not increase through trials, nor were they based on the outcomes experienced in previous trials. However, when we considered their initial preferences for the human actors, we observed a significant shift in preference for the skilful actor. Our subjects also looked preferentially at the skilful over the unskilled actor when both simultaneously manipulated a container. We observed substantial individual variation and species differences in choice and looking behaviours. While the cognitive mechanisms (impression formation vs outcome-based process) underlying these social decisions are still unclear, our findings indicate that Tonkean macaques and brown capuchins used social information about the actors skills to inform their decisions.

animal behavior and cognition↗

bioRxiv2025

Patterns of sleeping site use of Guinea baboon parties (Papio papio)

Sleeping site use in primates is thought to be influenced by multiple factors, including resource availability and competition, predation risk, and the risk of parasitic infection. While previous research has highlighted the importance of these factors, few studies have examined sleeping site use among multiple groups of non-territorial species with overlapping home ranges. Here, we investigated the sleeping site use of Guinea baboons (Papio papio) in Simenti, Senegal. We used locational data for four years of several baboon parties sharing the same range. We assessed the distribution of sleeping sites within the local habitat mosaic, the proximity of sleeping sites to those of co-occurring parties and the impact of food availability and predator presence at the landscape level on the distance between parties sleeping sites on the same night. We further investigated patterns of sleeping site use of parties across time. We found that the vast majority of sleeping sites were in the gallery forest along the perennial Gambia River, likely due to the availability of tall trees. Guinea baboons slept in close spatial proximity (>50m) to at least one other party regardless of food availability and predator presence. Patterns of sleeping site use showed no evidence of predator or parasite avoidance. Thus, Guinea baboons in Simenti likely use the abundantly available sleeping sites opportunistically rather than being driven by intergroup competition or strategies for predator avoidance or reduction of the risk of parasite infection.

ecology↗